This invention relates to the preparation of 2-hydroxy-4-methylthiobutanoic acid or salts thereof and more particularly to an improved process for preparing an aqueous product comprising 2-hydroxy-4-methylthiobutanoic acid.
2-hydroxy-4-methylthiobutanoic acid, commonly referred to as the hydroxy analog of methionine and also known as 2-hydroxy-4-methylthiobutyric acid or HMBA, is an analog of the essential amino acid methionine. Methionine analogs such as HMBA are effective in supplying methionine for nutritional uses, particularly as a poultry feed supplement. To efficiently produce feed supplements containing HMBA, the hydrolysis must be sufficiently complete.
HMBA has been manufactured by various processes involving hydrolysis of 2-hydroxy-4-methylthiobutanenitrile (also known as HMBN or 2-hydroxy-4-methylthiobutyronitrile and hereinafter xe2x80x9cHMBNxe2x80x9d or xe2x80x9cnitrilexe2x80x9d). HMBA has been produced as a racemic D,L-mixture by hydrolyzing HMBN with a mineral acid, precipitating the acid residue by addition of an alkaline earth hydroxide or carbonate, and recovering a salt of HMBA from the aqueous phase by evaporative crystallization, as described, for example, in Blake et al U.S. Pat. No. 2,745,745.
British Patent No. 915,193 describes a process for the preparation of the calcium salt of HMBA in which HMBN is hydrolyzed to HMBA in a continuous back-mixed reactor using a dilute sulfuric acid solution, and HMBA is separated from the reaction liquor by extraction with an ether. Because of the use of a continuous back-mixed reaction system, the process of the British patent may not achieve complete conversion of HMBN or amide intermediate to HMBA. The presence of significant unreacted material is undesirable where a liquid HMBA product is to be made.
Recently, HMBA has been commercially produced by hydrolyzing HMBN with sulfuric acid to form a high quality hydrolyzate containing HMBA, extracting HMBA from the hydrolyzate, and recovering the HMBA from the extract as described by Ruest et al. U.S. Pat. No. 4,524,077. In the process, HMBN is mixed with sulfuric acid having a strength of between about 50% and about 70% by weight on an organic-free basis at a temperature of between about 25xc2x0 C. and about 65xc2x0 C. To control the rate of reaction, the HMBN is preferably added to the acid over a period of about 30 to about 60 minutes. Under the preferred conditions, substantial conversion of the nitrile to 2-hydroxy-4-methylthiobutanamide (also known as 2-hydroxy-4-methylthiobutyramide and hereinafter xe2x80x9camidexe2x80x9d) takes place in a period of between about one-half hour and about one and one-half hours. Thereafter, the amide is converted to HMBA by further hydrolysis at a temperature within the range of between about 70xc2x0 C. and 120xc2x0 C. Final hydrolysis of the amide to the acid is carried out in sulfuric acid having an initial strength of between about 30% and about 50% by weight on a organic-free basis. To provide the preferred acid strength, the acid phase is diluted by adding water before heating the reaction mixture. Under conditions of relatively dilute acid strength and increased temperature, the amide is converted to the acid within a period of approximately one and one-half to three hours. In carrying out the hydrolysis, approximately one mole of sulfuric acid per mole of the HMBN feed is used, with an acid excess of 0 to 10%, preferably 0 to 5%, providing satisfactory results. Ruest et al. describe a batch process and state that a batch process is preferred to ensure that the hydrolysis reaction is carried substantially to completion. If a continuous reaction system is utilized, Ruest et al. describe that it should be designed and operated to assure essentially complete conversion. For example, continuous operation could be implemented in a plug flow tubular reactor or cascaded stirred tank system. A single back-mixed reactor is described by Ruest et al. as providing adequate conversion only at residence times that would generally be considered unacceptable for commercial production.
Hernandez et al. U.S. Pat. No. 4,912,257 describes a process in which HMBA is produced by sulfuric acid hydrolysis of HMBN in a single step. HMBN is fed to an acidification vessel where it is mixed with 98% sulfuric acid at an acid/nitrile molar ratio between 0.5 and 2 to form a reaction mixture containing 20-50% by weight sulfuric acid. The mixture is agitated and cooled to 50xc2x0 C. in a continuous addition loop for 30-60 minutes as the reaction mixture is produced batchwise. The reaction mixture is then fed to a hydrolysis reactor and heated to a temperature of between 60xc2x0 C. and 140xc2x0 C. for five minutes to six hours while applying a slight vacuum to the reactor. The process described by Hernandez et al. is said to produce HMBA by hydrolysis of the acidified HMBN solution in a single step unlike the two step hydrolysis processes known in the art.
In order to provide a high quality hydrolyzate product containing maximum HMBA and minimal nitrile and amide components, high conversion of HMBN and 2-hydroxy-4-methylthiobutyramide to HMBA must be obtained. Batch production of HMBA generally provides high conversion. However, conventional batch processes for producing HMBA have several drawbacks. The productivity of a batch process is limited by batch turnaround time. Additionally, the quality of HMBA hydrolyzate can deviate between batches because reaction conditions can vary as each batch is produced. Filling and emptying of the batch reactor and non-steady state conditions cause vapor emissions that must be treated before release. The equipment required for the prior art processes is costly. Sulfuric acid and water are mixed in an acid dilution tank to form diluted sulfuric acid feed. A heat exchanger is required to remove the heat of dilution that is generated within the tank. The tank, heat exchanger, pump and recirculation loop must be of corrosion resistant construction.
Among the several objects of the present invention are the provision of an improved process for the preparation of HMBA; the provision of such a process that can be operated in a continuous mode; the provision of such a process that can be operated with high productivity; the provision of such a process that can significantly reduce capital and maintenance costs as compared to conventional processes; the provision of such a process that affords improved control of reaction conditions as compared to conventional batch hydrolysis systems; the provision of such a process that reduces the vapor emissions as compared to conventional batch systems; the provision of such a process that eliminates the need for separate sulfuric acid dilution, in particular, the provision of such a process that can be operated using a concentrated sulfuric acid feed stream without prior dilution; the provision of such a process that effects essentially complete conversion of HMBN to HMBA; and the provision of such a process that can produce HMBA of consistent quality for use in the preparation of animal feed supplements.
These and other objects are obtained through a process for the preparation of HMBA or a salt thereof including introducing a mineral acid into a nitrile hydrolysis reactor comprising a continuous stirred tank reactor, and introducing 2-hydroxy-4-methylthiobutanenitrile into the nitrile hydrolysis reactor. 2-hydroxy-4-methylthiobutanenitrile is continually hydrolyzed within the nitrile hydrolysis reactor to produce a nitrile hydrolysis reactor product stream containing 2-hydroxy-4-methylthiobutanamide. The nitrile hydrolysis reactor product stream is continuously introduced into an amide hydrolysis flow reactor. 2-hydroxy-4-methylthiobutanamide is continuously hydrolyzed within the amide hydrolysis flow reactor to produce a finished aqueous hydrolyzate product containing 2-hydroxy-4-methylthiobutanoic acid. 2-hydroxy-4-methylthiobutanoic acid is recovered from the finished aqueous hydrolyzate product.
In another embodiment of the invention, 2-hydroxy-4-methylthiobutanoic acid or a salt thereof is produced by a process in which 2-hydroxy-4-methylthiobutanenitrile, concentrated sulfuric acid having a strength of between about 70% by weight and about 99% by weight, and water are concurrently introduced into a vessel in which 2-hydroxy-4-methylthiobutanenitrile is hydrolyzed. 2-hydroxy-4-methylthiobutanenitrile is hydrolyzed within the vessel to produce an aqueous hydrolysis mixture containing 2-hydroxy-4-methylthiobutanamide. 2-hydroxy-4-methylthiobutanamide is hydrolyzed to produce a finished aqueous hydrolyzate product containing 2-hydroxy-4-methylthiobutanoic acid. 2-hydroxy-4-methylthiobutanoic acid is recovered from the finished aqueous hydrolyzate product.
Yet another embodiment of the present invention is directed to an apparatus for use in a process for the preparation of HMBA. The apparatus includes a first continuous stirred tank reactor for the continuous hydrolysis of 2-hydroxy-4-methylthiobutanenitrile in the presence of a mineral acid to produce an aqueous hydrolysis mixture containing 2-hydroxy-4-methylthiobutanamide. The apparatus also includes an amide hydrolysis flow reactor for the continuous hydrolysis of 2-hydroxy-4-methylthiobutanamide with sulfuric acid to produce a finished aqueous hydrolyzate product containing 2-hydroxy-4-methylthiobutanoic acid.
Another embodiment of the invention is directed to a process for the preparation of 2-hydroxy-4-methylthiobutanoic acid or a salt thereof that includes introducing 2-hydroxy-4-methylthiobutanenitrile and an aqueous mineral acid into an aqueous hydrolysis mixture comprising 2-hydroxy-4-methylthiobutanamide, mineral acid, and unreacted 2-hydroxy-4-methylthiobutanenitrile. The 2-hydroxy-4-methylthiobutanenitrile in the aqueous hydrolysis mixture is hydrolyzed in a continuous nitrile hydrolysis reactor comprising a back-mixed reaction zone and a circulation zone in fluid flow communication with the back-mixed reaction zone. The circulation zone comprises a circulating line. The aqueous hydrolysis mixture is continuously circulated in a circulating stream that is withdrawn from the back-mixed reaction zone, passed through the circulation zone and returned to the back-mixed reaction zone. The circulating stream as withdrawn from the back-mixed reaction zone contains unreacted 2-hydroxy-4-methylthiobutanenitrile. A portion of the aqueous hydrolysis mixture is removed from a forward flow port in the circulation zone to form a nitrile hydrolysis reactor product stream. The nitrile hydrolysis reactor product stream is transferred to an amide hydrolysis flow reactor. The nitrile hydrolysis reactor product stream is diluted with water at a point downstream of the forward flow port to provide a finishing reaction stream. The 2-hydroxy-4-methylthiobutanamide contained in the finishing reaction stream is hydrolyzed in the amide hydrolysis flow reactor to produce a finished aqueous hydrolyzate product containing 2-hydroxy-4-methylthiobutanoic acid. The sum of the residence time of the circulating stream in the circulation zone upstream of the forward flow port and the residence time of the nitrile hydrolysis reactor product stream downstream of the forward flow port prior to dilution is sufficient to substantially extinguish residual 2-hydroxy-4-methylthiobutanenitrile prior to the dilution of the nitrile hydrolysis reactor product stream.